Background: We report herein the synthesis of a novel dicationic boron dipyrromethene
derivative (compound 3) which is symmetrically substituted with two
trimethylammonium styryl groups.
Methods: The antibacterial photodynamic activity of compound 3 was determined
against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including
four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC
BAA-44), two mutant strains [AAC(6’)-APH(2”) and RN4220/pUL5054], and ten nonduplicate
clinical strains of hospital- and community-associated MRSA. Upon light irradiation,
the minimum bactericidal concentrations of compound 3 were in the range of
1.56-50 μM against all the sixteen MRSA strains. Interestingly, compound 3 was not only
more active than an analogue in which the ammonium groups are not directly connected
to the n-conjugated system (compound 4), but also showed significantly higher (p <
0.05) antibacterial potency than the clinically approved photosensitizer methylene blue.
The skin irritation of compound 3 during topical application was tested on human 3-D
skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM.
In the murine MRSA infected wound study, the colony forming unit reduction of compound
3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared
to other test groups except for the positive control.
Conclusion: In conclusion, the present study provides a scientific basis for future development
of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA